The long-term goal of the Principal Investigator is the exploration of three questions: (1) What is the role of angiogenesis in tumor growth? (2) How is tumor angiogenesis mediated? (3) How can tumor angiogenesis bbe inhibited? The principal investigator has recently discovered a new class of steroids which inhibit angiogenesis in the presence of heparin. These are named "angiostatic" steroids. There is a sub-set of these steroids which have no other known function except for the inhibition of angiogenesis. Angiostatic steroids are normally present at low levels in the circulation, and they can now be made synthetically. The overall objective of this grant proposal is two-fold: (1) to delineate the mechanism of action of angiostatic steroids at the cellular and molecular level; and (2) to test these compounds in tumor-bearing mice, so that a Phase I clinical trial can be designed. An additional objective is to test our hypothesis that the high survival rate and low metastatic rate in patients with a thin cutaneous melanoma (e.g., less than 0.76 mm), is because these lesions are avascular.